CD4⁺ T cells play critical roles during chronic viral infections, but the factors that regulate these responses remain incompletely defined. During chronic infection of mice with lymphocytic choriomeningitis virus clone 13 (LCMV13), the TNFR family member GITR plays a critical CD4⁺ T cell-intrinsic role in allowing T cell accumulation and viral control. Previously, RNA sequencing of GITR^+/+ and GITR^-/- T cells sorted from the spleen of mice at day 3 of LCMV13 infection identified the chemokine receptor CX3CR1 as increased by GITR signaling in CD4⁺ T cells. In this study, we evaluated the role of CX3CR1 on CD4⁺ T cells during LCMV13 infection. CX3CR1 expression is induced on Ag-specific CD4⁺ T cells upon Ag stimulation, and GITR signaling further increases the level of CX3CR1 expression. CX3CR1 marks the most differentiated T-bet^hi, Th1 effector population. Adoptively transferred CX3CR1^-/- SMARTA cells had slightly reduced expression of T-bet and IFN-γ per cell compared with their CX3CR1^+/+ counterparts but showed no deficit in accumulation in the spleen, lung, or liver. In mixed-radiation chimeras reconstituted with CX3CR1^+/+ and CX3CR1^-/- bone marrow, CX3CR1^+/+ CD4⁺ T cells showed a marginal deficit in tissue-resident memory T cell numbers compared with the CX3CR1^-/- T cells. CX3CR1 may limit acquisition of the tissue-resident memory T cell phenotype because of its effects on increasing T-bet expression, albeit these small effects are unlikely to be of major biological significance. Taken together, these studies show that CX3CR1 marks the most highly differentiated CD4⁺ Th1 effector population but is largely dispensable for CD4⁺ T cell responses during chronic viral infection.

#	Concept	H-Index	Publications	Citations
1	Medicine	2	2	66
2	Cell Biology	2	2	66
3	Immunology	2	2	66
4	Autoimmune Disease	2	2	66
5	Autoimmunity	2	2	66

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